Developmental regulation of expression of two major gene families was studied:globin genes and HMG 14(a nd b) and 17 genes. The former represents a differentiated function restricted to erythrocytes whereas the latter genes are constitutively expressed as an essential component of cellular chromatin. A. Globin genes. Expression of the epsilon globin gene is restricted to the primitive erythrocyte, which circulates only early in chick embryogenesis (day 1-7). The promoter has been sequenced and putative control regions are being analyzed by in vitro footprooting and gel mobility shift assays. The extracts used for these analyses are derived from erythrocytes obtained at different stages of development spanning the time when the epsilon gene is fully active to the adult chicken, when all genes are totally inactive. These regions of differential binding within the epsilon promoter are also being analyzed for functional activity by linkage to a reporter gene and subsequent transfection into primary erythrocytes. B. HMG 14 (a and b) and 17. To establish this system we investigated various parameters related to expression of these genes in erythrocytes during embryogenesis: pulse-labeled protein, steady state mRNA, nuclear run-ons that analyze only newly synthesized transcripts, and chromatin structure of the genes themselves. Our results suggest that the individual genes of the HMG family are differentially expressed in development. HMG 14a, in particular, is restricted to the primitive (early) erythrocyte whereas HMG 14b and 17 are maximally expressed only later, in the definitive erythrocyte, but not in the reticulocyte.